RESUMEN
Synthesis and antiparasitic activity vs T. cruzi and L. donovani of a series of 9-thioaryl acridines are reported. A convenient correlation between molecular structure and biological activity is proposed. Results not only agree with the classical interactions of acridines with DNA but also suggest possible role of charge transfer complexes.
Asunto(s)
Tripanocidas/síntesis química , Trypanosoma/efectos de los fármacos , Acridinas/síntesis química , Acridinas/farmacología , Animales , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Relación Estructura-Actividad Cuantitativa , Tripanocidas/farmacologíaRESUMEN
The synthesis of several acridinic thioethers is described. Compounds prepared were tested in vitro as potential drugs against the opportunistic infection known as cryptosporidiosis. With a view to predict activity, the quantitative structure-activity relationships were investigated. Correlations between experimental data and either log P or pKa are discussed.
Asunto(s)
Acridinas/síntesis química , Coccidiostáticos/síntesis química , Cryptosporidium parvum/efectos de los fármacos , Acridinas/farmacología , Acridinas/uso terapéutico , Animales , Animales Recién Nacidos , Bovinos , Línea Celular , Coccidiostáticos/farmacología , Coccidiostáticos/uso terapéutico , Criptosporidiosis/tratamiento farmacológico , Criptosporidiosis/parasitología , Cryptosporidium parvum/crecimiento & desarrollo , Heces/parasitología , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Relación Estructura-ActividadRESUMEN
A set of 9-thioalkylacridinones, has been prepared and investigated "in vitro" against T. cruzi. Structure-antiparasitic activity relationships are detailed with a view to identify the major structural parameters for the activity under consideration.
Asunto(s)
Acridinas/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Acridinas/química , Acridinas/clasificación , Animales , Antiprotozoarios , Técnicas In Vitro , Ratones , Relación Estructura-Actividad , Tripanocidas/químicaRESUMEN
The synthesis of 1-amino-10-alkyl-9-acridinones 4 and 5 and of homologous 9-thio-acridinones 7 and 8 are described. Similarly, the synthesis of 1-nitro-4-(2'-aminoethylamino)-9-acridinones 13 and 15, is described. Compound 4 was used as starting material for the preparation of 10-alkyl-9-acridinone dimers 6, bridged with an alpha,omega-diamido chain. Compound 15 was selected for biological investigations on pathogenic parasite strains, and a promising antiamoebic activity could be shown.
Asunto(s)
Acridinas/síntesis química , Aminoacridinas/síntesis química , Antiprotozoarios/síntesis química , Acanthamoeba/efectos de los fármacos , Acridinas/farmacología , Acridinas/toxicidad , Aminoacridinas/farmacología , Aminoacridinas/toxicidad , Animales , Antiprotozoarios/farmacología , Antiprotozoarios/toxicidad , Linfocitos T CD4-Positivos/efectos de los fármacos , Leishmania donovani/efectos de los fármacos , Masculino , Ratones , Trypanosoma cruzi/efectos de los fármacosRESUMEN
New acridinonic derivatives, which are hydroxy- and methoxy-substituted in positions 1, 4, and 1,4 were prepared with a view to obtain antiparasitic drugs. These compounds were tested against Trypanosoma cruzi strains and their capability of interacalation into DNA was determined. Nucleus substitutions, DNA binding, and trypanocidal activities have been correlated.